Posterior Reversible Encephalopathy Syndrome in a Patient with Variegate Porphyria: A Case Report.

Variegate porphyria (VP) is one of the groups of rare inherited disorders of hemoglobin synthesis called Porphyria. It has two distinct manifestations, that is, those of cutaneous and nervous system. Posterior reversible encephalopathy syndrome (PRES) is a rare complication of porphyria. It occurs due to vasogenic edema in white matter of predominantly parieto-occipital lobes, characterized by headache, visual disturbances, altered mental state, hypertension, and seizures. We report a child diagnosed with VP who presents with clinical signs and radiological manifestations suggestive of PRES. To our knowledge this has never been reported in a case of VP and only twice been reported in another type of porphyria. A 12-year-old pre-pubertal boy already diagnosed with VP presents with seizure, visual disturbance, altered mental status, headache, and hypertension. Initial brain magnetic resonance imaging (MRI) revealed bilateral increased signal intensity in parieto-occipital region. Neurological opinion suggested that the symptoms experienced by the patient seem to be a complication of porphyria. Treatment was to control hypertension and prevent use of any aggravating agents. Follow-up MRI after two weeks revealed interval reduction in disease process. Diagnosis of PRES was thus confirmed. PRES should be considered in patients presenting with symptoms typical of encephalitis/meningitis/acute disseminated encephalomyelitis in a patient suffering from porphyria. Early diagnosis is key to quick improvement and prevention of complications. Though rare in pre-pubertal patients, it should be kept as a possibility especially when patients present with hypertension. Care should be taken to not use any drugs that can trigger PRES.

The Genetic Legacy of the Indian Ocean Slave Trade: Recent Admixture and Post-admixture Selection in the Makranis of Pakistan.

From the eighth century onward, the Indian Ocean was the scene of extensive trade of sub-Saharan African slaves via sea routes controlled by Muslim Arab and Swahili traders. Several populations in present-day Pakistan and India are thought to be the descendants of such slaves, yet their history of admixture and natural selection remains largely undefined. Here, we studied the genome-wide diversity of the African-descent Makranis, who reside on the Arabian Sea coast of Pakistan, as well that of four neighboring Pakistani populations, to investigate the genetic legacy, population dynamics, and tempo of the Indian Ocean slave trade. We show that the Makranis are the result of an admixture event between local Baluch tribes and Bantu-speaking populations from eastern or southeastern Africa; we dated this event to ∼300 years ago during the Omani Empire domination. Levels of parental relatedness, measured through runs of homozygosity, were found to be similar across Pakistani populations, suggesting that the Makranis rapidly adopted the traditional practice of endogamous marriages. Finally, we searched for signatures of post-admixture selection at traits evolving under positive selection, including skin color, lactase persistence, and resistance to malaria. We demonstrate that the African-specific Duffy-null blood group-believed to confer resistance against Plasmodium vivax infection-was recently introduced to Pakistan through the slave trade and evolved adaptively in this P. vivax malaria-endemic region. Our study reconstructs the genetic and adaptive history of a neglected episode of the African Diaspora and illustrates the impact of recent admixture on the diffusion of adaptive traits across human populations.

Association of the ACE-II genotype with the risk of nephrotic syndrome in Pakistani children.

Nephrotic syndrome is a common pediatric glomerular disease associated with heavy proteinuria. Since, the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is a putative genetic risk factor for NS, in this study, ACE (I/D) polymorphism was analyzed in 268 NS and 223 control samples by a PCR-based method. The genotypic and allelic frequencies were determined and the association between ACE I/D polymorphism and NS was evaluated. The frequency distribution of the II, ID and DD genotypes was 82 (30.6%), 128 (47.8%) and 58 (21.6%) in the NS patients and 9 (4.0%), 171 (76.7%) and 43 (19.3%) in the control samples respectively. In the Pakistani pediatric NS population, the II genotypic and allelic frequencies were found to be significantly associated with the disease (OR=6.755; C.I=3-14.9). No significant association was found between this polymorphism and the response to standard steroid therapy. Thus, in contrast to reports from other parts of the world, the II genotype was found to be significantly associated with NS in the Indian and Malay populations and in the Pakistani population described here. To our knowledge, this is the first report from Pakistan describing the association of the ACE I/D polymorphism with pediatric NS. On the basis of these results, it is suggested that analysis of the ACE (I/D) polymorphism should be performed for the early diagnosis in the high risk NS patients in South Asia.